Search

Background The number of patients with Chagas disease residing in Europe has increased significantly due to migration flows. Globally, Chagas cardiomyopathy has worse prognosis than other types of dilated cardiomyopathies and about 30% of patients develop cardiac involvement after a variable latency period (10–30 years). However, there is lack of data regarding the evolution of patients with Chagas disease living in a non-endemic area and potential early predictors of disease progression. OBJETIVE To describe the natural course of Chagas disease, the incidence rate of transformation into cardiac form and to assess if early predictors of myocardial involvement translate into a worse long-term prognosis in our non-endemic cohort. Methods Clinical and echocardiographic follow-up was performed in 202 individuals from endemic areas of Chagas disease. At baseline, electrocardiogram, BNP and a comprehensive echocardiography including diastolic function and longitudinal myocardial strain were performed. Four different groups were defined: healthy controls (N=77); Chagas indeterminate form (positive serology, normal ECG and left ventricle (LV) dimensions and LV ejection fraction (>50%) and no segmental abnormalities, N=92); Chagas patients with abnormal ECG but normal LV dimensions and motility (N=15); and Chagas patients with LV diameter>55 mm or LV ejection fraction Results Mean age was 37±9 and 34% were male. Median follow-up was 69 months (range 1 to 147). The primary endpoint occurred in a total of 17 (8.4%) individuals: 5 (5.4%) in the Indeterminate group; 3 (20%) in the abnormal ECG group; and 9 (50%) in the group with abnormal LV dimension or motility, with no events among controls (long-rank test Conclusions Conversion from the indeterminate to Chagas cardiomyopathy in our cohort was approximately 1.1%/year, but it may happen directly with contractility disturbances. BNP and comprehensive echocardiography may help to early detect disease progression. Figure 1. Distribution of patients and KM curves Funding Acknowledgement Type of funding source: None

The immigration of Latin American women of childbearing age has spread the congenital transmission of Chagas disease to areas of nonendemicity, and the disease is now a worldwide problem. Some European health authorities have implemented screening programs to prevent vertical transmission, but the lack of a uniform protocol calls for the urgent establishment of a new strategy common to all laboratories. Our aims were to (i) analyze the trend of passive IgG antibodies in the newborn by means of five serological tests for the diagnosis and follow-up of congenital Trypanosoma cruzi infection, (ii) assess the utility of these techniques for diagnosing a congenital transmission, and (iii) propose a strategy for a prompt, efficient, and cost-effective diagnosis of T. cruzi infection. In noninfected newborns, a continuous decreasing trend of passive IgG antibodies was observed, but none of the serological assays seroreverted in any the infants before 12 months. From 12 months onwards, serological tests achieved negative results in all the samples analyzed, with the exception of the highly sensitive chemiluminescent microparticle immunoassay (CMIA). In contrast, in congenitally infected infants, the antibody decline was detected only after treatment initiation. In order to improve the diagnosis of congenital T. cruzi infection, we propose a new strategy involving fewer tests that allows significant cost savings. The protocol could start 1 month after birth with a parasitological test and/or a PCR. If negative, a serological test would be carried out at 9 months, which if positive, would be followed by another at around 12 months for confirmation.

Background Brain natriuretic peptide (BNP) and novel echocardiographic techniques such as speckle-tracking and a comprehensive evaluation of diastolic function can detect early myocardial involvement in patients with Chagas disease. However, there is lack of longitudinal studies that can confirm whether this early myocardial involvement translates into a worse prognosis. Purpose To assess if early myocardial involvement detected by BNP or a comprehensive echocardiographic evaluation was associated with future events in Chagas disease. Methods 182 consecutive individuals from endemic areas who underwent T. cruzi screening where prospectively included from 2007 to 2014. ECG, BNP and a comprehensive echocardiography including diastolic function and longitudinal myocardial strain were performed. Four different groups were defined: healthy controls (N=77); Chagas indeterminate form (positive serology, normal ECG and left ventricle (LV) diameter (50%) and no segmental abnormalities, N=88); Chagas patients with abnormal ECG but normal LV dimensions and motility (N=7); and Chagas patients with LV diameter>55 mm or LV ejection fraction Results Mean age was 37±9 and 34% were male. Median follow-up was 63 months (range 1 to 137). The primary endpoint occurred in a total of 11 (10%) individuals: 2 (2.4%) in the Indeterminate group; 3 (43%) in the abnormal ECG group; and 6 (46%) in the group with abnormal LV dimension or motility, with no events among controls (long-rank test Cumulative survival without events Conclusions Outcome was significantly more frequent in Chagas patients with abnormalities in ECG or standard echocardiography. In early forms of the disease, myocardial involvement detected by BNP or a comprehensive echocardiography was associated with prognosis, and may help to individualize treatment and follow-up.

For treating Chagas disease (CD), a current worldwide health problem, only benznidazole and nifurtimox have been approved to be used. In both cases, unwanted drug-related adverse events (ADRs) are frequent when these drugs are used in adults in the chronic stage. The main objective of this study was to establish benznidazole ADRs and their relationship to serum concentrations in patients with chronic Trypanosoma cruzi infection in order to perform more accurate dosages to minimize ADRs. A total of 54 patients were recruited over 12 months. Of these 54 patients, 53 (98%) experienced at least one ADR during follow-up, and the overall average ADR incidence was 2.4 episodes/patient/month. Benznidazole treatment was discontinued in 11 patients, 7 among them due to severe adverse effects. The mean duration of treatment before withdrawal was 11 days. Benznidazole serum concentrations were recorded on days 15, 30, 45, and 60 of follow-up and evaluated according to clinical and epidemiological variables and ADR severity. No relationship was found between the benznidazole serum concentration and the ADRs. The mean (standard deviation) trough serum benznidazole concentrations (all below 20 mcg/ml) on days 15, 30, 45, and 60 were 6.4 (1.9), 6.1 (1.8), 6.2 (2.2), and 5.7 (1.7) μg/ml, respectively. Benznidazole serum concentrations do not appear to be related to the appearance of serious ADRs. Further, well-controlled studies are necessary to establish the optimal regimen for benznidazole in adults with chronic CD.

Trypanosoma cruzi, the causative agent of Chagas disease, is divided into six Discrete Typing Units (DTUs): TcI–TcVI. We aimed to identify T. cruzi DTUs in Latin-American migrants in the Barcelona area (Spain) and to assess different molecular typing approaches for the characterization of T. cruzi genotypes. Seventy-five peripheral blood samples were analyzed by two real-time PCR methods (qPCR) based on satellite DNA (SatDNA) and kinetoplastid DNA (kDNA). The 20 samples testing positive in both methods, all belonging to Bolivian individuals, were submitted to DTU characterization using two PCR-based flowcharts: multiplex qPCR using TaqMan probes (MTq-PCR), and conventional PCR. These samples were also studied by sequencing the SatDNA and classified as type I (TcI/III), type II (TcII/IV) and type I/II hybrid (TcV/VI). Ten out of the 20 samples gave positive results in the flowcharts: TcV (5 samples), TcII/V/VI (3) and mixed infections by TcV plus TcII (1) and TcV plus TcII/VI (1). By SatDNA sequencing, we classified the 20 samples, 19 as type I/II and one as type I. The most frequent DTU identified by both flowcharts, and suggested by SatDNA sequencing in the remaining samples with low parasitic loads, TcV, is common in Bolivia and predominant in peripheral blood. The mixed infection by TcV–TcII was detected for the first time simultaneously in Bolivian migrants. PCR-based flowcharts are very useful to characterize DTUs during acute infection. SatDNA sequence analysis cannot discriminate T. cruzi populations at the level of a single DTU but it enabled us to increase the number of characterized cases in chronically infected patients. Fil: Abras, Alba. Universidad de Barcelona; España. Universidad de Girona; España. Barcelona Centre for International Health Research; España Fil: Gállego, Montserrat. Universidad de Barcelona; España. Barcelona Centre for International Health Research; España Fil: Muñoz, Cármen. Hospital de la Santa Creu i Sant Pau; España. Universitat Autònoma de Barcelona; España Fil: Juiz, Natalia Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Ramirez Gomez, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Cura, Carolina Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres” ; Argentina Fil: Tebar, Silvia. Universidad de Barcelona; España. Barcelona Centre for International Health Research; España Fil: Fernández Arévalo, Ana. Universidad de Barcelona; España. Barcelona Centre for International Health Research; España. Hospital de la Santa Creu i Sant Pau; España Fil: Pinazo, María Jesús. Barcelona Centre for International Health Research; España Fil: de la Torre, Leonardo. Barcelona Centre for International Health Research; España Fil: Posada, Elizabeth. Barcelona Centre for International Health Research; España Fil: Navarro, Ferran. Universitat Autònoma de Barcelona; España. Hospital de la Santa Creu i Sant Pau; España Fil: Espinal, Paula. Hospital de la Santa Creu i Sant Pau; España Fil: Ballart, Cristina. Universidad de Barcelona; España. Barcelona Centre for International Health Research; España Fil: Portús, Montserrat. Universidad de Barcelona; España Fil: Gascón, Joaquim. Barcelona Centre for International Health Research; España Fil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina

Due to international migration, Chagas disease, endemic in Latin America, has become more common in non-endemic areas. Chronic Chagas disease can cause damage to the digestive system leading to constipation. However, a range of factors influences constipation and a better understanding of the role of non-Chagas related factors is required to improve management of Chagas-related digestive problems. This study explores perceptions of constipation and changes in food and exercise habits amongst Bolivians in Barcelona, Spain. Bolivian migrants attending the Tropical Medicine Unit (Hospital Clínic, Barcelona) were interviewed about their food habits in Spain and Bolivia, migratory experience, work and leisure activities. Chagas seropositive participants also received radiological examinations. Bolivian migrants experienced dietary changes, influenced by work-related factors, which included reductions in quantities of food and liquid consumed. Almost half the participants reported changes in digestive rhythm since arriving in Spain. Constipation, which was common, in some cases was only recounted during interviews. Bolivian migrants’ constipation may be associated with chronic Chagas disease or migration-related dietary changes. Careful questioning using the Rome III criteria is however required to ensure its diagnosis. Radiological studies are also required to confirm the role of Chagas disease and identify potentially serious intestinal damage.

A strategic challenge facing all governments today is how to deliver services effectively and efficiently. At one time, they thought that they could meet this challenge by exploiting technology and going the E-government route with the promise of single-window, integrated, intelligent service delivery. Very quickly, however, they had to accept the fact that they would have to overcome a multitude of obstacles and that individual and corporate clients often preferred to receive service in traditional ways. As a result, the delivery of public services is becoming increasingly multichannel: over the counter, by mail and telephone, over the Internet, via text and television, etc. There is therefore a need to identify some kind of model for managing this highly complex new phenomenon effectively and efficiently. By conducting research in the field with the help of case studies and international benchmarking, it was possible to identify the main variables in the degree of effectiveness and efficiency of multi...

Thromboembolic events were described in patients with Chagas disease without cardiomyopathy. We aim to confirm if there is a hypercoagulable state in these patients and to determine if there is an early normalization of hemostasis factors after antiparasitic treatment. Ninety-nine individuals from Chagas disease-endemic areas were classified in two groups: G1, with T.cruzi infection (n = 56); G2, healthy individuals (n = 43). Twenty-four hemostasis factors were measured at baseline. G1 patients treated with benznidazole were followed for 36 months, recording clinical parameters and performance of conventional serology, chemiluminescent enzyme-linked immunosorbent assay (trypomastigote-derived glycosylphosphatidylinositol-anchored mucins), quantitative polymerase chain reaction, and hemostasis tests every 6-month visits. Prothrombin fragment 1+2 (F1+2) and endogenous thrombin potential (ETP) were abnormally expressed in 77% and 50% of infected patients at baseline but returned to and remained at normal levels shortly after treatment in 76% and 96% of cases, respectively. Plasmin-antiplasmin complexes (PAP) were altered before treatment in 32% of G1 patients but normalized in 94% of cases several months after treatment. None of the patients with normal F1+2 values during follow-up had a positive qRT-PCR result, but 3/24 patients (13%) with normal ETP values did. In a percentage of chronic T. cruzi infected patients treated with benznidazole, altered coagulation markers returned into normal levels. F1+2, ETP and PAP could be useful markers for assessing sustained response to benznidazole., Author Summary The manuscript describes the results of a study whose aim was to assess the tendency to coagulate in people suffering from a parasitic infection frequent in Latin America named T. cruzi infection or Chagas disease, by the study of several coagulation factors. According to the state of the art in this topic, specific treatment for Chagas disease is recommended in recent (acute) and late (chronic) stages of the infection. The effectiveness of current available drugs in the chronic stage of infection is still a topic of debate due to inconsistent results across studies and a lack of early measurable parameters of response to specific treatment. Another aim of this study was to determine if the presence of an upregulated procoagulative activity in plasma in people suffering T. cruzi infection could be used as potential marker that indicates therapeutic response in people at chronic stage of the disease. The results of this study suggest that measurements of alterations of procoagulative activity may be useful to indicate specific treatment for T. cruzi chronically infected patients and new data concerning early response to treatment biomarkers.

Chagas disease is a parasitic infection that leads to a significant public health problem in countries where the disease is endemic and where it is nonendemic. Benznidazole is the most commonly used drug for the etiological treatment of Chagas disease. Patients treated with benznidazole suffer frequent adverse drug reactions. Although arthralgia is common, arthritis has been reported as a very rare side effect. The objective of this study was to describe arthritis in a cohort of Trypanosoma cruzi -infected patients treated with benznidazole.

Introduction: Chagas disease is a common condition among Latin American immigrants living in Spain. Material and methods: An immunochromatographic test was used for Chagas disease screening in 148 patients from Latin America and the results were compared with those of 2 ELISA techniques. Results: The test had a sensitivity of 92.5%, a specificity of 96.8%, and a coefficient of agreement with the 2 ELISA techniques of 0.9. Conclusions: The specificity of the test assayed suffices for Chagas disease screening, but the sensitivity needs to be improved before it can be used for this purpose.

Set on its current course thirty years ago by Herbert Simon’s notions of bounded rationality and sequential stages, the research literature of organizational decision making is claimed in this paper to have suffered from three major limitations labeled reification, dehumanization, and isolation. In particular, it has been stuck along a continuum between the cerebral rationality of the stage theories at one end and the apparent irrationality of the theory of organized anarchies at the other. This paper seeks to open up decision making in three respects. First, the concept of “decision” is opened up to the ambiguities that surround the relationship between commitment and action. Second, the decision maker is opened up to history and experience, to affect and inspiration, and especially to the critical role of insight in transcending the bounds of cerebral rationality. Third, the process of decision making is opened up to a host of dynamic linkages, so that isolated traces of single decisions come to be seen as interwoven networks of issues. The paper concludes with a plea to open up research itself to the development of richer theory on these important processes.

Background Conventional serological tests, using total soluble proteins or a cocktail of recombinant proteins from T. cruzi as antigens, are highly sensitive for Chagas disease diagnosis. This type of tests, however, does not seem to be reliable tools for short- and medium-term monitoring of the evolution of patients after antiparasitic treatment. The aim of the present study was to search for immunological markers that could be altered in the sera from Chagas disease patients after benznidazole treatment, and therefore have a potential predictive diagnostic value. Methods We analyzed the reactivity of sera from chagasic patients during different clinical phases of the disease against a series of immunodominant antigens, known as KMP11, PFR2, HSP70 and Tgp63. The reactivity of the sera from 46 adult Chronic Chagas disease patients living in a non-endemic country without vector transmission of T. cruzi (15 patients in the indeterminate stage, 16 in the cardiomiopathy stage and 16 in the digestive stage) and 22 control sera from non-infected subjects was analyzed. We also analyzed the response dynamics of sera from those patients who had been treated with benznidazole. Results Regardless of the stage of the sickness, the sera from chagasic patients reacted against KMP11, HSP70, PFR2 and Tgp63 recombinant proteins with statistical significance relative to the reactivity against the same antigens by the sera from healthy donors, patients with autoimmune diseases or patients suffering from tuberculosis, leprosy or malaria. Shortly after benznidazole treatment, a statistically significant decrease in reactivity against KMP11, HSP70 and PFR2 was observed (six or nine month). It was also observed that, following benznidazole treatment, the differential reactivity against these antigens co-relates with the clinical status of the patients. Conclusions The recombinant antigens KMP11, PFR2, Tgp63 and HSP70 are recognized by Chagas disease patients' sera at any clinical stage of the disease. Shortly after benznidazole treatment, a drop in reactivity against three of these antigens is produced in an antigen-specific manner. Most likely, analysis of the reactivity against these recombinant antigens may be useful for monitoring the effectiveness of benznidazole treatment., We thank Fundacion Mundo Sano España for supporting Chagas research in CRESIB. This study was supported by grants P08-CVI-04037PAI (Junta de Andalucía), BFU2010-1670 from Plan Nacional I+D+i (MICINN), RD06/0021/0014 - ISCIII-RETIC (MICINN, Spain) and FEDER. MJP, EP and JG were supported by grant 2009SGR385 from the Department d'Universitats, Recerca i Societat de la Informació de la Generalitat de Catalunya, Spain.

Background/Aims The epidemiology of Chagas disease, until recently confined to areas of continental Latin America, has undergone considerable changes in recent decades due to migration to other parts of the world, including Spain. We studied the prevalence of Chagas disease in Latin American patients treated at a health center in Barcelona and evaluated its clinical phase. We make some recommendations for screening for the disease. Methodology/Principal Findings We performed an observational, cross-sectional prevalence study by means of an immunochromatographic test screening of all continental Latin American patients over the age of 14 years visiting the health centre from October 2007 to October 2009. The diagnosis was confirmed by serological methods: conventional in-house ELISA (cELISA), a commercial kit (rELISA) and ELISA using T cruzi lysate (Ortho-Clinical Diagnostics) (oELISA). Of 766 patients studied, 22 were diagnosed with T. cruzi infection, showing a prevalence of 2.87% (95% CI, 1.6–4.12%). Of the infected patients, 45.45% men and 54.55% women, 21 were from Bolivia, showing a prevalence in the Bolivian subgroup (n = 127) of 16.53% (95% CI, 9.6–23.39%). All the infected patients were in a chronic phase of Chagas disease: 81% with the indeterminate form, 9.5% with the cardiac form and 9.5% with the cardiodigestive form. All patients infected with T. cruzi had heard of Chagas disease in their country of origin, 82% knew someone affected, and 77% had a significant history of living in adobe houses in rural areas. Conclusions We found a high prevalence of T. cruzi infection in immigrants from Bolivia. Detection of T. cruzi–infected persons by screening programs in non-endemic countries would control non-vectorial transmission and would benefit the persons affected, public health and national health systems., Author Summary Chagas disease is a parasitic infection caused by the protozoan Trypanosoma cruzi, and is becoming an emerging health problem in non-endemic areas because of growing population movements. The clinical manifestations of chronic T. cruzi infection include the latent form (the indeterminate chronic form), the cardiac form, the digestive or cardiodigestive form, and sudden death. Therefore, many diagnoses of Chagas disease are based on epidemiological suspicion rather than on clinical signs and symptoms. This study showed that the prevalence of Chagas disease in Latin American patients attending at a health center in Barcelona is 2,87% and the highest prevalence was found among Bolivian patients (16,53%). All the infected patients were in a chronic phase of Chagas disease. Detection of T. cruzi–infected persons by screening programs in non-endemic countries would control non-vectorial transmission and would benefit the persons affected, public health and national health systems. The data obtained in this study and the experiences described elsewhere suggest that it is advisable to perform Chagas disease screening in non-endemic countries on all patients from continental Latin America who: (1)have a suggestive epidemiologic history, (2)are pregnant, (3)are immunosuppressed, (4)have symptoms suggestive of Chagas disease, or (5)request screening.

Background Chagas' disease is becoming a public health problem in Europe because of migratory movements. Cardiac magnetic resonance (CMR) has emerged as a non-invasive tool to assess cardiac tissue characteristics. There is scarce data available on CMR in patients with Chagas' disease. Objective To describe CMR findings in patients with Chagas' disease living in a non-endemic area focusing on differentiation from other cardiomyopathies and relation with clinical status. Methods and results Sixty-seven Chagas' disease patients divided into 3 groups—group 1 (indeterminate form: positive serology without ECG or 2D-echocardiographic abnormalities; N =27), group 2 (ECG abnormalities of Chagas' disease but normal 2D-echocardiography; N =19), and group 3 (regional wall motion abnormalities, LV end-diastolic diameter >55mm or LV ejection fraction N =21)—were studied. The presence of wall motion abnormalities and delayed enhancement (DE) by CMR was more frequent in the inferolateral and apical segments. DE distribution in the myocardial wall was heterogeneous (subendocardial 26.8%, midwall 14.0%, subepicardial 22.6%, and transmural 36.0% of total segments with DE) and related to larger cardiac chambers and worse systolic function. Conclusion Pattern of DE in Chagas' disease may mimic that of both ischemic and nonischemic cardiomyopathies, with especial predilection for the apical and inferolateral segments of the left ventricle. These findings support that myocardial involvement in chronic Chagas' cardiomyopathy (CCC) may be due to both microvascular disturbances and chronic myocarditis and may favor CCC in the differential diagnosis of patients with compatible epidemiological history and heart failure of uncertain etiology.

Background: Chagas disease is endemic in Latin America, affecting 16–18 million people with more than 100 million exposed to risk of infection. Its etiological agent is Trypanosoma cruzi. To date, benznidazole is the only treatment of Chagas disease available in Europe. Methods: A high-performance reversed-phase isocratic liquid chromatographic method for benznidazole analysis in human plasma is described. The mobile phase consists of 60% ultrafiltered water and 40% acetonitrile. Samples were precipitated with trichloroacetic acid (0.3 M) (1/1, v/v). The injection volume was 100 μL. Benzocaine was used as internal standard. Results: The assay was linear over a benznidazole concentration range of 1.6–100 μg/mL. The method showed good agreement of results (n=15): inaccuracy (5.6%), intra- and inter-day variability (1.1% and 3.9%, respectively), recovery (94.9%), limit of detection (0.8 μg/mL), lower limit of quantitation (1.6 μg/mL) and acceptable stability over 24 h in the auto-sampler. Only 25 samples (58%) showed values within the therapeutic range. Three samples were subtherapeutic and 15 were in the toxic range. Conclusions: The method offers a fast and simple approach to determining benznidazole in human plasma which could be of use in pharmacokinetic and safety studies.

Migration is a channel through which Chagas disease is imported, and vertical transmission is a channel through which the disease is spread in non-endemic countries. This study presents the economic evaluation of Chagas disease screening in pregnant women from Latin America and in their newborns in a non endemic area such as Spain. The economic impact of Chagas disease screening is tested through two decision models, one for the newborn and one for the mother, against the alternative hypothesis of no screening for either the newborn or the mother. Results show that the option “no test” is dominated by the option “test”. The cost effectiveness ratio in the “newborn model” was 22 €/QALYs gained in the case of screening and 125 €/QALYs gained in the case of no screening. The cost effectiveness ratio in the “mother model” was 96 €/QALYs gained in the case of screening and 1675 €/QALYs gained in the case of no screening. Probabilistic sensitivity analysis highlighted the reduction of uncertainty in the screening option. Threshold analysis assessed that even with a drop in Chagas prevalence from 3.4% to 0.9%, a drop in the probability of vertical transmission from 7.3% to 2.24% and with an increase of screening costs up to €37.5, “test” option would still be preferred to “no test”. The current study proved Chagas screening of all Latin American women giving birth in Spain and of their infants to be the best strategy compared to the non-screening option and provides useful information for health policy makers in their decision making process.

Chagas’ disease is an emerging public health problem in areas where the disease is not endemic. Treatment with benznidazole has shown efficacy in the acute stage of the disease, but its efficacy in the chronic stage remains controversial, and unwanted side effects are more frequent and severe in adults than in children. This study describes the profile of side effects of benznidazole in a cohort of Trypanosoma cruzi -infected patients in a European country.

Introduction Chagas disease remains a major cause of mortality in several countries of Latin America and has become a potential public health problem in non-endemic countries as a result of migration flows. Cardiac involvement represents the main cause of mortality, but its diagnosis is still based on nonspecific criteria with poor sensitivity. Early identification of patients with cardiac involvement is desirable, since early treatment may improve prognosis. This study aimed to assess the role of diastolic dysfunction, abnormal myocardial strain and elevated brain natriuretic peptide (BNP) in the early identification of cardiac involvement in Chagas disease. Methodology/Principal Findings Fifty-four patients divided into 3 groups—group 1 (undetermined form: positive serology without ECG or 2D-echocardiographic abnormalities; N = 32), group 2 (typical ECG abnormalities of Chagas disease but normal 2D-echocardiography; N = 14), and group 3 (regional wall motion abnormalities, left ventricular [LV] end-diastolic diameter >55 mm or LV ejection fraction 37 pg/ml) were noted in 0%, 13%, 29% and 63% in controls and groups 1 to 3, respectively. Half of patients in the undetermined form had impaired relaxation patterns, whereas half of patients with ECG abnormalities suggestive of Chagas cardiomyopathy had normal diastolic function. In group 1, BNP levels were statistically higher in patients with diastolic dysfunction as compared to those with normal diastolic function (27±26 vs. 11±8 pg/ml, p = 0.03). Conclusion/Significance In conclusion, the combination of diastolic function and BNP measurement adds important information that could help to better stratify patients with Chagas disease., Author Summary Chagas disease remains a major cause of morbidity and mortality in several countries of Latin America and has become a potential public health problem in countries where the disease is not endemic as a result of migration flows. Cardiac involvement represents the main cause of mortality, but its diagnosis is still based on nonspecific criteria with poor sensitivity. Early identification of patients with cardiac damage is desirable, since early treatment may improve prognosis. Diastolic dysfunction and elevated brain natriuretic peptide levels are present in different cardiomyopathies and in advanced phases of Chagas disease. However, there are scarce data about the role of these parameters in earlier forms of the disease. We conducted a study to assess the diastolic function, regional systolic abnormalities and brain natriuretic peptide levels in the different forms of Chagas disease. The main finding of our investigation is that diastolic dysfunction occurs before any cardiac dilatation or motion abnormality. In addition, BNP levels identify patients with diastolic dysfunction and Chagas disease with high specificity. The results reported in this study could help to early diagnose myocardial involvement and better stratify patients with Chagas disease.

Seccion de Medicina Tropical, Centro de Salud Internacional, Hospital Cĺinic i Provincial, Centre de Recerca en Salut Internacional de Barcelona (CRESIB), Barcelona, Espana Consulta de Salud Internacional, Servicio de Enfermedades Infecciosas, Hospitales Universitarios Virgen del Rocio, Sevilla, Espana Servicio de Gastroenteroloǵia, Hospital Cĺinic i Provincial, Barcelona, Espana Unidad de Salud Internacional, Hospital General de Valencia, Valencia, Espana Servicio de Radiodiagnostico, CDIC, Hospital Cĺinic i Provincial, Barcelona, Espana Unitat de Medicina Tropical i Salut Internacional Drassanes, Institut Catal a de la Salut (ICS), Barcelona, Espana Centro de Investigaciones en Microbioloǵia y Parasitoloǵia Tropical, Facultad de Ciencias, Departamento de Ciencias Biologicas, Universidad de los Andes, Bogot a, Colombia Gastroenteroloǵia, Hospital La Fe, Valencia, Espana Seccion de Medicina Tropical, Hospital Carlos III, Madrid, Espana Instituto de Gastroenteroloǵia de la Goiânia, Universidad Federal de Goi as, Goiânia, Goias, Brazil Unidad de Medicina Tropical de Hospital de Poniente, Aguadulce (Almeŕia), Espana Instituto de Gastroenteroloǵia Boliviano Japon es, Cochabamba, Bolivia Facultad de Medicina, Universidad Mayor de San Simon, Cochabamba, Bolivia Servicio de Medicina Interna, Hospital General Universitario de Alicante, Alicante, Espana Unitat de Medicina Tropical i Salut Internacional Drassanes, Barcelona, Espana

We performed a prospective screening for Trypanosoma cruzi infection in 1350 Latin American pregnant women and their offspring in Barcelona, Spain. The rate of seroprevalence was 3.4%, and 7.3% of the newborns were infected. Routine screening and management programs in maternity wards may be warranted.

Chagas disease is a common condition among Latin American immigrants living in Spain.An immunochromatographic test was used for Chagas disease screening in 148 patients from Latin America and the results were compared with those of 2 ELISA techniques.The test had a sensitivity of 92.5%, a specificity of 96.8%, and a coefficient of agreement with the 2 ELISA techniques of 0.9.The specificity of the test assayed suffices for Chagas disease screening, but the sensitivity needs to be improved before it can be used for this purpose.

Background Chagas disease is no longer limited to Latin America and is becoming frequent in industrialised countries in Europe and United States. Methods A descriptive study of Latin American immigrants in Barcelona attending two centres for imported diseases during a period of 3 years. The main outcome was the identification of Trypanosoma cruzi-infected individuals in a non-endemic country and the characterization of their clinical and epidemiological features. Results A total of 489 Latin American patients participated in the study. Forty-one percent were infected by T. cruzi, and the most frequent country of origin was Bolivia. All T. cruzi infected patients were in chronic stages of infection. 19% of cases had cardiac disorders and 9% had digestive disorders. Conclusions A high percentage of participants in this study were infected by T. cruzi and various factors were found to be associated to the infection. It is important to improve clinical and epidemiological knowledge of T. cruzi infection in non-endemic countries and to develop appropriate screening and treatment protocols in these settings.

Objectifs Etablir l’interet du transit colique avec marqueurs dans l’etude de la constipation a la phase chronique de la maladie de Chagas. Materiels et methodes Le lavement baryte et le transit colique avec marqueurs sont realises a 18 emigrants latino-americains diagnostiques de maladie de Chagas avec constipation (emission de moins de trois selles par semaine). Resultats Les lavements barytes etaient normaux chez 2 patients (11,11 %), 12 (66,66 %) presentaient un dolichocolon et 4 (22,22 %) un dolichomegacolon. Le transit colique avec marqueurs a ete pathologique dans seulement 3 malades (16,66 %). Conclusion Il existe une claire association entre la clinique de constipation el les donnees radiologiques du lavement baryte. Par contre, les resultats du transit colique avec marqueurs semblent peu fiables.

Objectifs Souligner l’interet des explorations barytees dans la caracterisation radiologique des manifestations digestives a la phase chronique de la maladie de Chagas. Materiels et methodes Le transit œsophagien minute et le lavement baryte sont realises a 32 emigrants latino-americains diagnostiques de maladie de Chagas avec symptomatologie digestive. Resultats Les etudes radiologiques ont ete normales sur 3 patients (9,4 %) et une anse sigmoidienne deroulee est observee sur 5 (16 %). Deux malades (6,2 %) presentaient alteration de la motilite œsophagique et pathologie du colon synchronique (1 dolicocolon et 1 dolicomegacolon) et 22 (68,1 %) alteration colique isolee (19 dolicocolon et 3 dolicomegacolon). Conclusion L’etude radiologique digestive est seulement necessaire sur les patients avec maladie de Chagas qui presentent symptomatologie et l’affection colique est la plus frequente.

The aim of the present study was to build a population pharmacokinetic (popPK) model to characterize benznidazole (BNZ) pharmacokinetics in adults with chronic Chagas disease. This study was a prospective, open-label, single-center clinical trial approved by the local ethics committee. Patients received BNZ at 2.5 mg/kg of body weight/12 h (Abarax, Elea Laboratory, Argentina) for 60 days. Plasma BNZ samples were taken several times during the study and analyzed by high-performance liquid chromatography with UV-visible detection (HPLC-UV). The popPK analysis was done with NONMEMv.7.3. Demographic and biological data were tested as covariates. Intraindividual, interoccasion, and residual variabilities were modeled. Internal and external validations were completed to assess the robustness of the model. Later on, simulations were performed to generate BNZ concentration-time course profiles for different dosage regimens. A total of 358 plasma BNZ concentrations from 39 patients were included in the analysis. A one-compartment PK model characterized by clearance (CL/ F ) and the apparent volume of distribution ( V / F ), with first-order absorption ( K a ) and elimination, adequately described the data (CL/ F , 1.73 liters/h; V / F , 89.6 liters; and K a , 1.15 h −1 ). No covariates were found to be significant for CL/ F and V / F . Internal and external validations of the final model showed adequate results. Data from simulations revealed that a dose of 2.5 mg/kg/12 h might lead to overexposure in most patients. A lower dose (2.5 mg/kg/24 h) was able to achieve trough BNZ plasma concentrations within the accepted therapeutic range of 3 to 6 mg/liter. In summary, we developed a population PK model for BNZ in adults with chronic Chagas disease. Dosing simulations showed that a BNZ dose of 2.5 mg/kg/24 h will adequately keep BNZ trough plasma concentrations within the recommended target range for the majority of patients. (This study has been registered at EudraCT under number 2011-002900-34 and at ClinicalTrials.gov under number NCT01755403.)

Background: Benznidazole is one of the two most effective antiparasitic drugs for Chagas' disease treatment. However, knowledge about its toxicity profile is mostly based on post-marketing observational studies. Objectives: Our study combines data from two prospective clinical trials designed to assess the safety of the drug newly produced by ELEA Laboratories (Abarax(R)). Methods: Eligible participants were selected using a consecutive sampling strategy in the CINEBENZ and BIOMARCHA studies between 2013 and 2016 (EUDRACT 2011-002900-34 and 2012-002645-38, respectively, and clinicaltrials.gov NCT01755403 and NCT01755377, respectively). Enrolled subjects received treatment with 5 mg/kg/day benznidazole orally in two divided doses for 8 weeks and were followed up fortnightly. Results: We observed 305 adverse reactions in 85 of 99 participants (85.9%). Each patient had a median of three adverse reactions, 89.5% were mild and the median duration was 12 days. Most adverse reactions appeared in the first month of treatment except arthritis and peripheral neuropathy. Twenty-six patients did not complete treatment: 2 were withdrawn, 1 for ectopic pregnancy and 1 for epilepsy relapse due to cysticercosis; 2 were lost to follow-up; and 22 were owing to adverse reactions, two of them severe. We observed some unexpected adverse reactions that have not been described previously, such as psychiatric symptoms, erectile dysfunction, menstrual cycle alterations and lung infiltration. Conclusions: There is a very high frequency of adverse reactions to benznidazole. Most adverse reactions are mild, but the treatment burden is significant and unexpected reactions are not rare. Severe reactions are uncommon, but they can be life-threatening. Further studies are necessary to optimize treatment.

Immunosuppression, which has become an increasingly relevant clinical condition in the last 50 years, modifies the natural history of Trypanosoma cruzi infection in most patients with Chagas disease. The main goal in this setting is to prevent the consequences of reactivation of T. cruzi infection by close monitoring. We analyze the relationship between Chagas disease and three immunosuppressant conditions, including a description of clinical cases seen at our center, a brief review of the literature, and recommendations for the management of these patients based on our experience and on the data in the literature. T. cruzi infection is considered an opportunistic parasitic infection indicative of AIDS, and clinical manifestations of reactivation are more severe than in acute Chagas disease. Parasitemia is the most important defining feature of reactivation. Treatment with benznidazole and/or nifurtimox is strongly recommended in such cases. It seems reasonable to administer trypanocidal treatment only to asymptomatic immunosuppressed patients with detectable parasitemia, and/or patients with clinically defined reactivation. Specific treatment for Chagas disease does not appear to be related to a higher incidence of neoplasms, and a direct role of T. cruzi in the etiology of neoplastic disease has not been confirmed. Systemic immunosuppressive diseases or immunosuppressants can modify the natural course of T. cruzi infection. Immunosuppressive doses of corticosteroids have not been associated with higher rates of reactivation of Chagas disease. Despite a lack of evidence-based data, treatment with benznidazole or nifurtimox should be initiated before immunosuppression where possible to reduce the risk of reactivation. Timely antiparasitic treatment with benznidazole and nifurtimox (or with posaconazole in cases of therapeutic failure) has proven to be highly effective in preventing Chagas disease reactivation, even if such treatment has not been formally incorporated into management protocols for immunosuppressed patients. International consensus guidelines based on expert opinion would greatly contribute to standardizing the management of immunosuppressed patients with Chagas disease.